Development of an optogenetic gene sensitive to daylight and its implications in vision restoration

Optogenetic gene-mediated therapy for restoring vision is thought to be a useful treatment for blind patients. However, light sensitivity achieved using this gene therapy is inferior to that of daylight vision. To increase light sensitivity, we designed three mutants using a bioinformatics approach. Nucleotide sequences encoding two sites in the extracellular loops (ex1, ex3) of mVChR1 close to simulated ion-conducting pathways were replaced by homologous amino acid-encoding sequences of ChR1 or ChR2. The light sensitivity of ex3mV1 was higher than that of mVChR1 at 405-617 nm. Visual responses were restored in Royal College of Surgeons rats with genetically degenerating photoreceptor cells transfected with ex3mV1Co, wherein transmembrane of sixth (TM6) in ex3mV1 was additionally replaced with the corresponding domain of CoChR; these rats responded to light in the order of mu W/mm(2). Thus, ex3mV1Co might be useful for the restoration of advanced visual function.

Automated summary

The research team has successfully increased the light sensitivity of optogenetic gene-mediated therapy by designing mutants, which were used to restore visual responses in rats with genetically degenerating photoreceptor cells. The results suggest that ex3mV1Co may be an effective method for restoring advanced visual function.